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β肾上腺素受体信号相关通路参与心功能不全患者心肌重构的机制(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2008年第1期
页码:
37-40，44
栏目:
临床研究
出版日期:
2008-01-20

文章信息/Info

Title:
β adrenoceptor signaling pathways and myocardium remodeling in patients with congestive heart failure
作者:
杨永健; 张鑫;  速晓华
成都军区总医院心血管内科，四川 成都 610083
Author(s):
YANG Yongjian;  ZHANG Xin;  SU Xiaohua
Department of Cardiology, General Hospital, Chengdu Military Area Command, Chengdu 610083, Sichuan, China
关键词:
心力衰竭; 充血性;  心肌;  受体; 肾上腺素能β
Keywords:
Heart failure;  congestive;  Myocardium;  Receptors;  adrenergic β
分类号:
R541.2
DOI:
-
文献标识码:
A
摘要:
目的 观察充血性心力衰竭（CHF）心肌组织肾上腺素受体β1、β2、β3mRNA表达及钙调神经磷酸酶（CaN）通路的变化水平与心肌重构的关系。方法 选择因瓣膜性心脏病接受二尖瓣置换术的CHF患者39例，正常健康人但因意外伤亡的器官捐献者8例。RTPCR检测心肌组织β1、β2、β3mRNA表达，免疫沉淀法检测心肌组织CaN、活化T细胞核因子(NFAT3）、锌指转录因子(GATA4)磷酸化及蛋白表达以及原癌基因cfos、c-myc蛋白表达。结果 CHF患者呈典型的重构心肌的病理改变。心肌组织β1受体mRNA表达吸光值（A）/β-actin比值，随心功能恶化呈逐渐降低的趋势， 与正常对照组相比较差异显著（P<0.05 或P<0.01）；各组间β2受体mRNA表达差异无统计学意义; 各CHF组β3受体mRNA表达随心功能恶化呈逐渐升高的趋势，与正常对照组相比差异显著（P<0.05 或P<0.01）。心肌组织CaN、GATA4磷酸化A/β-actin比值, 在各CHF组随心功能恶化而逐渐增高，与正常对照组相比差异显著（P<0.05 或P<0.01）; NFAT3磷酸化A /β-actin比值随心功能恶化而逐渐降低,与正常对照组相比差异显著（P<0.05 或P<0.01）。结论 β1受体mRNA表达减少及β3受体mRNA表达增加激活的CaN信号通路参与调节CHF心肌重构的病理过程。
Abstract:
AIM To investigate the alteration of expressions of β1, β2 and β3adrenoceptor mRNA and calcineurin (CaN) signal pathway in human myocardial tissue and to study the relationship between their alterations and myocardial remodeling in patients with congestive heart failure. METHODS Thirtynine patients with congestive heart failure (CHF) at different levels according to NYHA were randomly selected and 30 cases of healthy persons were enrolled as controls. Cardiac function parameters were measured by echocardiography. Pathologic and morphologic studies were conducted by optical microscope in 39 patients of mitral valve disease with CHF and 8 control subjects. mRNA expression of β1, β2 and β3adrenoceptor in myocardial tissue was analyzed by reverse transcriptasepolymerase chain reaction (RTPCR) and immunoprecitipation was used to assay the protein expression and phosphorylation of CaN, nuclear factor of activated T cells (NFAT3), zinc finger transcription factor (GATA4), and protein expression of cfos and cmyc in myocardial tissues. RESULTS Pathological changes of myocardial tissues in CHF with valve heart disease showed typical myocardial remodeling. The hypertrophy was dominant at the early stage of CHF, but at the end stage the characteristics included disordered alignment of the myocytes, the discontinuity and dissolving of cardiomyofibrills, destroyed subcellular organs, and the hyperplasia of interstitial tissues. β1adrenergic receptor mRNA expressions in myocardial tissue were significantly lower in patients with heart failure than those in control group (P<0.05 or P<0.01). β3adrenergic receptor mRNA expressions in myocardial tissues were significantly higher in patients with heart failure than those in control group (P<0.05 or P<0.01). No differences were observed in β2adrenergic receptor mRNA expressions among all the groups. Phosphorylation CaN and GATA4 in CHF groups were stronger than those in control group and were positively correlated to the levels of CHF (P<0.05 or P<0.01). On the contrary, phosphorylation of NFAT3in CHF groups was lower than that in control group and was negatively correlated to the levels of CHF (P<0.05 or P<0.01). CONCLUSION Both the lower expressions of β1adrenergic receptor mRNA and higher expressions of β3adrenergic receptor mRNA are involved in the pathogenesis process of myocardial remodeling by activation of CaN signal pathway.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2006-12-06.通迅作者：杨永健，副主任医师，博士，主要从事心肌重构信号转导机制研究Email: yangyongjian38@yahoo.com
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